Prevalence of KIR-B Haplotype and KIR Alloreactivity in Donors of Haploidentical Hematopoietic Cell Transplantation: A Single Center Study from India

印度单中心研究:单倍型相合造血干细胞移植供者中KIR-B单倍型和KIR同种异体反应的患病率

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Abstract

Alloreactive KIR-B haplotypes mediate potent anti-tumor and anti-microbial effects and can improve the prognosis of haploidentical hematopoietic cell transplantation (HHCT) but there is paucity of this data in the Indian population. We aimed to evaluate the prevalence of KIR-B haplotypes and their alloreactivity in HHCT donors at our center. A total of 119 individuals (haploidentical donors, (n = 93); and patients, n = 26) from 26 families were included in this study. The KIR genotyping of the donors and HLA-B, as well as HLA-C genotyping of donor-recipient pairs, was done by polymerase chain reaction with sequence-specific primer genotyping assay. The KIR B-content score of donors was calculated using the online donor KIR B-content group calculator of the Immuno Polymorphism Database (IPD)(www.ebi.ac.uk/ipd/kir/donor_b_content). The alloreactivity of KIR was determined using an online KIR ligand matching calculator of IPD (www.ebi.ac.uk/ipd/kir/matching/ligand). Haploidentical donors were siblings and parents in 64% and 36% of cases, respectively. The prevalence of KIR-A (A/A) and KIR-B haplotype (B/A or B/B) in donors was 21% (20/93) and 79% (73/93), respectively. The KIR-B content score was 0 in 21% (20/93), 1-2 in 66% (61/93), and 3-4 in 13% (12/93) of donors. Accordingly, donors were classified as better/best in 77% (20/26) and neutral in 23% (6/26) of screened families. The KIR alloreactivity was absent in 44% (41/93) of donors while it was present in the recipient-versus-donor direction in 21% (20/93), the donor-versus-recipient direction in 23% (21/93) and both directions in 12% (11/93) of donors. Our study shows that over two-thirds of donors have KIR-B haplotype and over two-thirds of families have killer-B content based better/best donors but KIR alloreactivity in GvH direction in approximately one-fourth of donors highlights the feasibility of alloreactive KIR-B haplotype-based selection of suitable donors for HHCT.

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